A method and device generally in the area of bioerodible controlled release systems for the delivery and administration of biologically active growth hormone.
The concept of using biodegradable polymeric matrix systems for the delivery and controlled release of drugs and therapeutically active agents has only recently been developed and demonstrated to be clinically useful. Active agents have conventionally been administered by the periodic application of dosages in the form of injections, pills, liquids or topical treatments such as ointments, creams, or sprays. Drugs administered by these methods are generally neither confined to the target area nor delivered in a linear, continuous manner. The result is evident in the variable levels of active agent both above and below the efficacy level, physical discomfort and expense in the case of repeated subcutaneous injections, and inconvenience due to the requirement of timely applications. The efficacy of treatment may also be compromised as a result of failure to fulfill the prescribed treatment regime due to negligence, lapse, or non-compliance.
Alternative methods of delivery which correct these deficiencies have been sought for years. Bioerodible polymeric matrix compositions hold much promise in the development of improved delivery systems. Several polymers have been used for this application, including poly(anhydrides), poly(lactic acid), poly(orthoesters), and ethylene vinyl acetate. Poly(anhydrides) have been found to produce superior release when linear, or zero order, release rates are desirable, using shapes that do not significantly change their surface area as a function of time.
An example of a biologically useful protein that is most effective when delivered continuously over extended periods of time is growth hormone. Unfortunately, this protein frequently aggregates and loses activity, making it difficult to deliver on a continuous basis.
A controlled release polymer implant system that has been developed to deliver growth hormone is described in European Patent Application No. 86305431.8. This system, however, has several drawbacks. For example, because the device is not biodegradable, the device must be removed after treatment. Furthermore, the polymer utilized to form the device is limited to those which do not bind to nor promote aggregation of the growth hormone. This limitation in the choice of the polymer also limits the range and extent of release of active agent. Polymers which might otherwise be desirable for reasons of release kinetics and duration, specifically polymers that are more hydrophilic or more hydrophobic in nature, cannot be used due to interactions with, or adverse influence upon, the active agent. The device is also limited to subcutaneous implantation in animals since use in humans would require post-treatment removal of the device.
It is therefore an object of the present invention to provide a biodegradable controlled release implantable device for controlled in vivo administration of growth hormone.
It is a further object of the present invention to provide a method and means for the stabilization of growth hormone in bioerodible polymeric matrices.
It is a still further object of the present invention to provide a method and means for modulating the rate of release of the stabilized polypeptidic agents from the bioerodible polymeric matrix.